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UniProtKB/Swiss-Prot Q5HYA8: Variant p.Ile833Thr

Meckelin
Gene: TMEM67
Variant information

Variant position:  833
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Type of variant:  Disease [Disclaimer]
The variants are classified into three categories: Disease, Polymorphism and Unclassified.
  • Disease: Variants implicated in disease according to literature reports.
  • Polymorphism: Variants not reported to be implicated in disease.
  • Unclassified: Variants with uncertain implication in disease according to literature reports. Evidence against or in favor of a pathogenic role is limited and/or conflicting.

Residue change:  From Isoleucine (I) to Threonine (T) at position 833 (I833T, p.Ile833Thr).
Indicates the amino acid change of the variant. The one-letter and three-letter codes for amino acids used in UniProtKB/Swiss-Prot are those adopted by the commission on Biochemical Nomenclature of the IUPAC-IUB.

Physico-chemical properties:  Change from medium size and hydrophobic (I) to medium size and polar (T)
The physico-chemical property of the reference and variant residues and the change implicated.

BLOSUM score:  -1
The score within a Blosum matrix for the corresponding wild-type to variant amino acid change. The log-odds score measures the logarithm for the ratio of the likelihood of two amino acids appearing by chance. The Blosum62 substitution matrix is used. This substitution matrix contains scores for all possible exchanges of one amino acid with another:
  • Lowest score: -4 (low probability of substitution).
  • Highest score: 11 (high probability of substitution).
More information can be found on the following page

Variant description:  In COACHS and JBTS6; found in a patient with Joubert syndrome that also carries mutation 1329-R--S-1332 Del in KIF7.
Any additional useful information about the variant.

Other resources:  
Links to websites of interest for the variant.



Sequence information

Variant position:  833
The position of the amino-acid change on the UniProtKB canonical protein sequence.

Protein sequence length:  995
The length of the canonical sequence.

Location on the sequence:   AENLCSQRGLVPNTDGQTFE  I AISNQMRQHYDRIHETLIRK
The residue change on the sequence. Unless the variant is located at the beginning or at the end of the protein sequence, both residues upstream (20) and downstream (20) of the variant will be shown.

Residue conservation: 
The multiple alignment of the region surrounding the variant against various orthologous sequences.

Human                         AENLCSQRGLVPNTDGQTFEIAISNQMRQHYDRIHETLIRK

Mouse                         AENLCSQRGLVPNTDGQTFQIAVSSQMRQHYDRIHETLTRR

Rat                           AENLCSQRGLVPNTDGQTFQIAVSSQMRQHYDRIHETLTRR

Sequence annotation in neighborhood:  
The regions or sites of interest surrounding the variant. In general the features listed are posttranslational modifications, binding sites, enzyme active sites, local secondary structure or other characteristics reported in the cited references. The "Sequence annotation in neighborhood" lines have a fixed format:
  • Type: the type of sequence feature.
  • Positions: endpoints of the sequence feature.
  • Description: contains additional information about the feature.

TypePositionsDescription
Chain 36 – 995 Meckelin


Literature citations

MKS3/TMEM67 mutations are a major cause of COACH Syndrome, a Joubert Syndrome related disorder with liver involvement.
Brancati F.; Iannicelli M.; Travaglini L.; Mazzotta A.; Bertini E.; Boltshauser E.; D'Arrigo S.; Emma F.; Fazzi E.; Gallizzi R.; Gentile M.; Loncarevic D.; Mejaski-Bosnjak V.; Pantaleoni C.; Rigoli L.; Salpietro C.D.; Signorini S.; Stringini G.R.; Verloes A.; Zabloka D.; Dallapiccola B.; Gleeson J.G.; Valente E.M.;
Hum. Mutat. 30:E432-E442(2009)
Cited for: VARIANTS COACHS ARG-130; LYS-372; GLN-440; SER-590; GLY-728; ARG-782; SER-820 AND THR-833;

Hypomorphic mutations in meckelin (MKS3/TMEM67) cause nephronophthisis with liver fibrosis (NPHP11).
Otto E.A.; Tory K.; Attanasio M.; Zhou W.; Chaki M.; Paruchuri Y.; Wise E.L.; Wolf M.T.F.; Utsch B.; Becker C.; Nuernberg G.; Nuernberg P.; Nayir A.; Saunier S.; Antignac C.; Hildebrandt F.;
J. Med. Genet. 46:663-670(2009)
Cited for: VARIANTS NPHP11 LEU-290; ARG-615; SER-821 AND ARG-821; VARIANTS JBTS6 44-GLN--ILE-995 DEL; 208-ARG--ILE-995 DEL; THR-252; ARG-615; ARG-821 AND THR-833;

Mutations in 3 genes (MKS3, CC2D2A and RPGRIP1L) cause COACH syndrome (Joubert syndrome with congenital hepatic fibrosis).
Doherty D.; Parisi M.A.; Finn L.S.; Gunay-Aygun M.; Al-Mateen M.; Bates D.; Clericuzio C.; Demir H.; Dorschner M.; van Essen A.J.; Gahl W.A.; Gentile M.; Gorden N.T.; Hikida A.; Knutzen D.; Ozyurek H.; Phelps I.; Rosenthal P.; Verloes A.; Weigand H.; Chance P.F.; Dobyns W.B.; Glass I.A.;
J. Med. Genet. 47:8-21(2010)
Cited for: VARIANTS COACHS ASN-99; ARG-130; GLN-172; THR-242; THR-252; VAL-257; SER-349; LEU-358; LYS-372; GLU-376; CYS-441; SER-485; CYS-513; ARG-615; LEU-637; THR-833; PRO-841 AND CYS-942; VARIANTS JBTS6 ARG-82 AND SER-82;

Mutations in KIF7 link Joubert syndrome with Sonic Hedgehog signaling and microtubule dynamics.
Dafinger C.; Liebau M.C.; Elsayed S.M.; Hellenbroich Y.; Boltshauser E.; Korenke G.C.; Fabretti F.; Janecke A.R.; Ebermann I.; Nurnberg G.; Nurnberg P.; Zentgraf H.; Koerber F.; Addicks K.; Elsobky E.; Benzing T.; Schermer B.; Bolz H.J.;
J. Clin. Invest. 121:2662-2667(2011)
Cited for: VARIANTS JBTS6 LEU-358 AND THR-833;

Disclaimer: Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. They are not in any way intended to be used as a substitute for professional medical advice, diagnostic, treatment or care.